Comparison of activated charcoal and ipecac syrup in prevention of drug absorption

The efficacy of activated charcoal and ipecac syrup in the prevention of drug absorption was studied in 6 healthy adult volunteers, using a randomized, cross-over design. Paracetamol 1000 mg, tetracycline 500 mg and aminophylline 350 mg were ingested on an empty stomach with 100 ml water. Then, after 5 or 30 min, the subjects ingested, either activated charcoal suspension (50 g charcoal), syrup of ipecac, or, only after 5 min, water 300 ml. Activated charcoal, given either after 5 or 30 min, significantly (p less than 0.01 or less 0.05) reduced the absorption of these 3 drugs measured, for example as AUC0-24 h. Syrup of ipecac caused emesis on each occasion, with a mean delay of 15 min. When ipecac was given 5 min after the drugs, its effect on absorption was significant, but when it was given after 30 min only the absorption of tetracycline was reduced. Activated charcoal was significantly (p less than 0.05) more effective than ipecac in reducing drug absorption when given at the same time points. In cases of acute intoxication, depending on the quality and quantity of the drugs ingested, the relative efficacy of charcoal and ipecac may be somewhat different from that observed in the present study. Despite its emetic action, however, ipecac syrup is not very effective in preventing drug absorption and, in general, activated charcoal should also be given after induced emesis or gastric lavage.     

Preserving the emetic effect of syrup of ipecac with concurrent activated charcoal administration: a preliminary study

Activated charcoal is reported to block the emetic effect of syrup of ipecac. Therefore, activated charcoal administration is commonly delayed until syrup of ipecac induced emesis is complete. The advantages of early administration of activated charcoal have been well documented. Preservation of the emetic effect of syrup of ipecac in the presence of activated charcoal may produce a synergistic effect by enhancing toxin elimination. A study was conducted in ten human volunteers to determine if activated charcoal prevents the emetic effect of syrup of ipecac when a temporal separation exists between administration of the two substances. Syrup of ipecac 60 ml plus water 480 ml was administered via an 18 French nasogastric tube followed by an aqueous slurry of activated charcoal 50 g five minutes later. Eight (80%) of the subjects had emesis in a mean time of 20.25 minutes (range 16-26 min). The total dose of activated charcoal was retained for a mean time of 6.75 minutes (range 0-17 min). Two subjects (20%) failed to have emesis. This study illustrates that activated charcoal may not completely block the emetic effect of syrup of ipecac.     

In vitro evidence for ipecac inactivation by activated charcoal.

The in vitro adsorption of the alkaloid emetine, a primary constituent of ipecac, on activated charcoal was studied. The results support the supposition that syrup of ipecac should not be given to counteract poisonings if activated charcoal is also to be administered.     

Effect of dose of charcoal on the absorption of disopyramide,indomethacin and trimethoprim by man

Summary The efficacy of various charcoal-to-drug ratios for the absorption of drugs was studied in 6 healthy volunteers and in vitro at two pHs. Disopyramide 200 mg, indomethacin 50 mg and trimethoprim 200 mg were ingested on an empty stomach with 100 ml water. After 5 min the subjects ingested a charcoal suspension in 300 ml — 2.5 g, 10 g, 25 g or 50 g of Norit A, or 10 g of PX-21, or water 300 ml only. Increasing the dose of activated charcoal from 2.5 g to 50 g reduced the gastrointestinal absorption of disopyramide and indomethacin from 30–40% to 3–5%, and that of trimethoprim from 10% to 1% of the respective controls. Disopyramide and trimethoprim were best adsorbed by charcoal in vitro at neutral and indomethacin at acid pH, but saturation of the adsorption capacity was apparent at charcoal-to-drug ratios less than 7.5. Combining the in vitro and in vivo results it can be concluded that the dose of activated charcoal to be given in acute intoxication should be as large as possible, because the drug history is often unknown.     

Effect of Ethanol and pH on the Adsorption of Drugs to Activated Charcoal: Studies in Vitro and in Man

Abstract: The effect of ethanol on the adsorption of aspirin, quinidine and amitriptyline to activated charcoal was studied in vitro at pH 1.2 and 7.0. The adsorption of these drugs was greatly dependent on the charcoal-drug ratio and on the pH. Ethanol (10%) significantly (P<0.001) increased the percentage of their unadsorbed fraction at both pHs in vitro. In six healthy volunteers activated charcoal (50 g), ingested 5 min. after aspirin (1000 mg) and quinidine sulfate (200 mg), reduced their bioavailability by about 70% (aspirin) and 99% (quinidine). A significant desorption of aspirin but not that of quinidine from charcoal was obvious on the second and third days and seemed to be related to the effect of pH. The absorption of ethanol was not significantly prevented by charcoal. The concomitant ingestion of alcohol (50 g) with drugs antagonized only slightly the ability of charcoal to reduce the absorption of aspirin and quinidine.     

Effect of activated charcoal on absorption and elimination of phenobarbitone,carbamazepine and phenylbutazone in man

Summary The effect of activated charcoal, given as a water suspension, on the absorption and elimination of phenobarbitone 200 mg, carbamazepine 400 mg and phenylbutazone 200 mg, was studied in five healthy volunteers, using a randomized crossover design. Absorption of the drugs was almost completely prevented (more than 95%) when charcoal 50 g was ingested within five minutes of taking the drugs. When activated charcoal was taken one hour after the drugs, the mean inhibition of drug absorption was considerably less and the inhibition was greatly dependent on the individual rate of absorption. The half-life of phenobarbitone was markedly shortened from a control value of 110±23 h to 19.8±1.0 h (P<0.05), with a corresponding increase in plasma clearance from 4.6 ml/min to 23 ml/min, when activated charcoal 118 g, in five divided doses was given between 10 and 48 h after ingestion of the drug. The half-life of carbamazepine was shortened by 45% (P<0.05) and the reduction in the half-life of phenylbutazone (30%) by charcoal, too, was statistically significant. The only side effect from use of the charcoal suspension was constipation, which occured in three subjects after repeated doses, and which was easily treated with lactulose if required. Although activated charcoal should be given as soon as possible, even its delayed use may be indicated, due to the slow absorption often seen in acute intoxication. The use of multiple doses of charcoal appears to be indicated as an additional treatment of certain severe intoxications to prevent the release of drugs from charcoal, and to increase their rate of elimination if they are secreted into the gut with subsequent reabsorption.     

Acupressure for prevention of emesis in patients receiving activated charcoal

OBJECTIVE: Vomiting after activated charcoal decontamination is problematic. Acupressure (traditional Chinese medicine) is an effective treatment for emesis, but has not been tested in overdose patients. We sought to determine (1) the incidence of emesis after activated charcoal and (2) the ability of acupressure to prevent emesis due to activated charcoal. METHODS: Consecutive overdose patients were enrolled in a preliminary, prospective study to determine the incidence of emesis after activated charcoal. Awake patients, > 18 years, received 1 g/kg activated charcoal orally or via nasogastric tube, and then observedfor 1 hour. These patients served as controls forpart 2 of the study, where acupressure bands were placed on overdose patients at the Nei-Guan P-6 point of both wrists prior to activated charcoal, followed by 1 hour observation. Exclusion criteria included: ipecac decontamination, antiemetic drug ingestion, antiemetic drug therapy within 1 hour of activated charcoal, or intubation. RESULTS: Eighty-one patients were included in the control group and 106 patients in the acupressure treatment group. Demographics and ingested substances were similar in both groups. 21/81 (25.9%) in the control group vomited and 15/106 (14.2%) in the acupressure group vomited. Acupressure reduced emesis by 46% (p = 0.043; chi2). Within the acupressure group, the median duration of prophylactic acupressure was 5 minutes in those patients without vomiting compared to 4 minutes in those patients with vomiting (NS; Wilcoxon rank sum test). CONCLUSION: The incidence of emesis after activated charcoal at our institution was 26%. Prophylactic acupressure reduced activated charcoal-induced vomiting by 46%. Investigators suggest 5 minutes of acupressure prior to activated charcoal.     

Effect of charcoal-drug ratio on antidotal efficacy of oral activated charcoal in man.

The effect of charcoal-drug ratio on the antidotal efficacy of oral activated charcoal was studied in six healthy volunteers in a randomized cross-over study and compared with the adsorption capacity of activated charcoal in vitro. Aminosalicylic acid (PAS) 1 g and 5 g were ingested on an empty stomach in 30 ml of water. Immediately afterwards the subjects ingested 50 g of activated charcoal in 300 ml of water or 300 ml of water only. PAS 10 g 20 g were only given with 50 g of activated charcoal administered immediately afterwards. The plasma concentrations and the cumulative excretion of PAS into urine were measured for 48 h. Increasing the dose of PAS from 1 g to 20 g reduced the antidotal efficacy of activated charcoal: at a charcoal-drug ratio of 50:1 under 5% of the dose was absorbed but at a ratio of 2.5:1 about 37%. These data correlated well to the saturation of adsorption capacity of charcoal in vitro. To minimize the possibility of saturation of the adsorption capacity of charcoal in acute intoxications where the amount and type of drug taken is usually unknown, large doses (50-100 g) of activated charcoal should be used.     

Effect of activated charcoal on absorption of tolbutamide and valproate in man

Summary The pharmacokinetics of indoramin (Baratol^?) have been studied in five male and five female healthy, middle-aged volunteers after intravenous administration (0.14 mg/kg). Elimination occurred in an apparently biexponential fashion with a mean elimination half-life of 4.0h (±0.25 SEM). The mean plasma clearance was 19.9 ml/min/kg (±1.32 SEM) and the mean volume of distribution 7.4 l/kg (±0.81 SEM). There were no significant differences in these parameters between male and female volunteers. Protein binding of indoramin ranged from 85.6% at 81 ng/ml to 72.2% at 129 μg/ml. Two classes of binding site were evident, with affinity constants of 6.85×10⁴M⁻¹ and 4.30×10³M⁻¹.     

Do gastric contents modify antidotal efficacy of oral activated charcoal?

The effect of food on the antidotal efficacy of activated charcoal was studied in six healthy volunteers, who ingested aspirin 1000 mg, mexiletine 200 mg and tolfenamic acid 400 mg in a randomized cross-over study. Activated charcoal 25 g, suspended in water, was administered 5 min or 60 min after the drugs were taken on an empty stomach or after a standard meal. The serum concentrations and the cumulative excretion into urine of the drugs were followed for 48 h. When the drugs were taken on an empty stomach, activated charcoal given 5 min or 60 min afterwards reduced the bioavailability of the drugs by 75-98% or 10-60%, respectively. Food moderately weakened the effect of activated charcoal administered 5 min after the drugs, but when the charcoal was given 1 h later the effect was still practically the same, the reduction of absorption varying in both cases in the range of 45-85%. Thus the efficacy of charcoal given 60 min after the drugs was better after a standard meal than on an empty stomach. Presence of food in the stomach of patients with drug overdosage modifies the efficacy of activated charcoal and gives it more time to adsorb drugs in the gastrointestinal canal, possibly by slowing gastric emptying rate.     

The preadministration of activated charcoal and aspirin absorption.

There is little information describing the effects of activated charcoal preadministration on drug absorption. This study was undertaken to determine the effect of activated charcoal preadministration at two different times on aspirin absorption. Fifteen volunteer subjects completed three study phases: 1) 975 mg aspirin alone, 2) 975 mg aspirin 30 min after 10 g activated charcoal, and 3) 975 mg aspirin 60 min after 10 g activated charcoal. Urine was collected for 48 h after the initiation of each study phase, and total aspirin recovery determined by HPLC. The aspirin recovery was 88.8% +/- 4.5% for the control phase, and 84.8% +/- 9.4% (Phase 1) and 85.8% +/- 12.6% (Phase 2) for the activated charcoal treatments (p > 0.05). These results suggest that activated charcoal administered 30 and 60 min prior to drug ingestion has little effect on drug absorption. Further studies of the effect of charcoal preadministration on the absorption of other drugs may provide useful information regarding factors important in determining activated charcoal efficacy.     

Rapid emesis from high-dose ipecac syrup in adults and children intoxicated with antiemetics or other drugs.

The effect of ipecac syrup as an emetic in adults as well as children who had ingested antiemetics or other drugs was evaluated. Adults or children over five years of age were given 30 ml of ipecac syrup followed by 360 ml of water; children aged one to five years were given 15 ml ipecac syrup followed by 240 ml of water. If emesis was not induced within 30 minutes, a second dose was administered. Of 232 patients studied (199 adults and 33 children), 188 (81%) vomited following the first dose, 34 (15%) required two doses and seven (3%) did not vomit. Of 63 patients who had ingested drugs with antiemetic properties, 51 (81%) vomited following the first dose, nine (14%) required a second dose and three (5%) did not vomit. The time from ipecac administration to the onset of emesis in all 232 patients averaged 24.2 minutes. Ipecac was successful in inducing rapid emesis in both adults and children who had ingested antiemetics or other drugs, probably as a result of its irritating effect on the gastric mucosa.     

Capacity of two forms of activated charcoal to adsorb nefopam in vitro and to reduce its toxicity in vivo

The adsorption of nefopam hydrochloride to two different charcoals was studied in vitro at pH 1.2 and 7.4. Both forms of activated charcoal effectively adsorbed nefopam, but the adsorption was significantly (p less than 0.001) more complete to PX-21 than to Norit A and the neutral pH favored adsorption over the acid pH. The unadsorbed fraction increased steeply when the charcoal-to-nefopam ratio was decreased below 5. In mice, the administration of Norit A and PX-21 (1700 mg/kg) significantly (p less than 0.001) increased the acute LD50 of nefopam hydrochloride, by 4.3 fold and 5.8 fold, respectively. The calculated amounts of free drug in the gastrointestinal tract are in good agreement with the observed LD50 values without charcoal when the free fractions at pH 1.2 and the corresponding charcoal-to-nefopam ratios in vitro are used in the calculations. The antagonism of charcoal to nefopam toxicity was confirmed in rats, too. At charcoal-to-nefopam ratios higher than those used in the present study, an even more effective reduction of toxicity is obvious. Therefore, immediate oral administration of a high dose (50-100 g) of activated charcoal is highly recommended to prevent nefopam absorption in acute intoxications in man, too.     

Attenuation of brain mitochondria oxidative damage by Albizia julibrissin Durazz: neuroprotective and antiemetic effects

Medicinal plants, as new drugs, are considered for treatment of insomnia, anxiety, depression, confusion, nausea, and vomiting symptoms. The current study aimed to evaluate the neuroprotective and antiemetic effects of Albizia. julibrissin Durazz. flower extract in the chickens. Emesis was induced by copper sulfate and ipecac (60 and 600?mg/kg, orally, respectively) and the methanolic extract (50, 100, and 200?mg/kg) were injected intraperitoneally (i.p.). Mitochondrial function, lipid peroxidation (LPO), protein carbonyl (PC) content, and catalase activity as biomarkers of oxidative damage were evaluated in the brain mitochondria. All doses of extract showed significant (p?<?0.001) antiemetic activity against induced emesis by copper sulfate and ipecac. Brain mitochondria function (by 50, 100, and 200?mg/kg of extract) were increased 48%, 85%, and 90% against emesis induced by ipecac and 32%, 18%, and 24% against emesis induced by copper sulfate, respectively. LPO and PC contents were significantly decreased after the administration of extract in emesis induced by copper sulfate and ipecac. A significant decrease (p?<?0.01) of CAT activity was observed in the extract (200?mg/kg) group in emesis induced by copper sulfate in chickens brain mitochondria. The present study suggests that the extract had antiemetic effects against emesis induced by copper sulfate and ipecac in young chickens via peripheral and central mechanisms. Neuroprotective effect of the extract could be due to the increase in bioactive compounds, plasma antioxidants, or direct free radical scavenging that could prevent lipid and protein alteration and impede the formation of oxidative damage.     

Prevention of amlodipine absorption by activated charcoal: effect of delay in charcoal administration

Aims The purpose of this study was to investigate the effect of activated charcoal on the absorption of amlodipine, with special reference to delayed charcoal administration.
Methods Thirty-two healthy volunteers, eight subjects in four parallel groups, ingested 10 mg of amlodipine on an empty stomach. Activated charcoal (25 g in 300 ml of water) was ingested either immediately afterwards or 2 h or 6 h after amlodipine, or amlodipine was ingested with 300 ml of water only (control). Plasma concentrations and the cumulative excretion of amlodipine into urine were measured by GC-MS for 96 h and 72 h, respectively. In addition, adsorption of amlodipine to charcoal was studied in vitro .
Results Activated charcoal administered immediately after amlodipine reduced the amlodipine AUC(0,96 h) and the 72-h urinary excretion by 99% ( P <0.0005). After a delay of 2 h in charcoal administration the AUC(0,96 h) was reduced by 49% ( P =0.001), but after a delay of 6 h the reduction was 15% only ( P =NS). At a charcoal: drug ratio of 5:1, about 90% of amlodipine was adsorbed by charcoal in vitro; at ratios of 10:1 and 20:1, adsorption was practically complete.
Conclusions Activated charcoal almost completely prevented amlodipine absorption when administered immediately after amlodipine ingestion. Charcoal also markedly reduced amlodipine absorption when given 2 h after amlodipine; in amlodipine overdose, administration of charcoal may be beneficial even later. We conclude that administration of activated charcoal is the method choice to prevent absorption of amlodipine in amlodipine overdose.     

In vitro adsorption of tilidine HCl by activated charcoal

In vitro studies were carried out in order to determine the adsorption of tilidine HCl, a narcotic analgesic, by activated charcoal (max. adsorption capacity 185.5 mg/g of charcoal). The path of the adsorption isotherms at pH 1.2 and 7.5 suggests that the in vivo adsorption of tilidine HCl may be increased when the drug passes from the stomach to the intestine, unless the intestinal content exerts a displacing effect. Nevertheless, the adsorption was dependent on the quantity of activated charcoal used, becoming more complete when the quantity of activated charcoal was increased. The effects of additives on the adsorption capacity of activated charcoal were also investigated in vitro. Ethanol, sorbitol and sucrose significantly reduced drug adsorption, while cacao powder, milk and starch had no effect on tilidine adsorption. At an acid pH, Federa Activated Charcoal significantly adsorbed more drug than either Norit A or Activated Charcoal Merck.     

Effects of resins and activated charcoal on the absorption of digoxin, carbamazepine and frusemide.

1. The interference of resins and activated charcoal with the absorption of digoxin, carbamazepine and frusemide was studied. 2. In a cross-over study consisting of four phases, single doses of colestipol hydrochloride (10 g), cholestyramine (8 g), activated charcoal (8 g) or water only were given to six healthy volunteers immediately after the simultaneous ingestion of digoxin (0.25 mg), carbamazepine (400 mg) and frusemide (40 mg). Plasma and urine concentrations of the test drugs and the urine volumes were determined up to 72 h. 3. The absorption of digoxin was not reduced by colestipol, moderately (30-40%, P less than 0.05) reduced by cholestyramine and greatly (96%) by charcoal. 4. The absorption of carbamazepine was not decreased by cholestyramine, slightly (10%) by colestipol and greatly (90%) by activated charcoal. 5. The absorption and the diuretic effect of frusemide were significantly diminished by all agents. The bioavailability was reduced by colestipol 80%, by cholestyramine 95% and by activated charcoal 99.5%. 6. The interference with the gastrointestinal absorption of most of the basic drugs by colestipol and cholestyramine seems to be minimal. On the other hand, the resins may seriously impair the absorption of certain acidic drugs, for example frusemide.     

Activated charcoal and the absorption of ferrous sulfate in rats

The treatment of iron poisoning has typically not included the administration of activated charcoal due to the lack of evidence supporting its efficacy. Several in vitro studies have demonstrated good adsorption of iron in a variety of pH ranges that were comparable to those found with other drugs for which activated charcoal is clinically used. This study was designed to determine whether activated charcoal altered the gastrointestinal absorption of toxic doses of iron as ferrous sulfate in an in vivo model. Seventy-five male Sprague-Dawley rats were randomly assigned into 5 groups: control given only distilled water; 100 mg elemental Iron and water; 1:1 charcoal to iron; 2:1 charcoal to iron; and 4:1 charcoal to iron. All treatments were administered consecutively by gavage within 5 min. Physiological measurements and blood samples were taken at 0, 1, 4 and 8 h after treatment. There were no consistent differences in physiological measurements among the 5 groups. Mean serum iron concentrations did not differ among Groups 2, 3, 4 and 5 at the 4 sampling times except at I h between Groups 4 and 5. The area under the curve for serum iron concentrations did not differ among the treatment groups. Activated charcoal did not alter the extent of iron absorption in the experimental model.     

The extent of drug-drug interaction between amlodipine and activated charcoal is attenuated by food intake in rats

Activated charcoal decreases gastrointestinal absorption of concomitantly administered drugs. The absorption of amlodipine (AML) was reported as almost completely attenuated by 25 g of activated charcoal under a fasted condition, but not affected by 2 g of activated charcoal under a fed condition. However, it is not clear whether this difference resulted from the food intake or the dose of activated charcoal. The aim of this study was to quantitatively evaluate the effect of food intake on drug interactions caused by adsorption to activated charcoal in the gastrointestinal tract in rats. The rats were orally administered 0.08 mg/kg of AML, with or without 33 mg/kg of activated charcoal, under the fasted or fed condition and the plasma concentration profiles of AML were monitored. For the fed group, the standard breakfast used in clinical studies was smashed and administered at a dose of 11 g/kg. The AUC value of AML under the fasted condition was significantly decreased to 24.8% by coadministration of activated charcoal. On the other hand, activated charcoal moderately decreased the AUC value of AML to 74.8% under the fed condition. These results suggest that the extent of drug interactions caused by activated charcoal is attenuated by food intake.     

Effect of ethanol and pH on the adsorption of acetaminophen (paracetamol) to high surface activated charcoal, in vitro studies

BACKGROUND: Paracetamol (acetaminophen) intoxication often in combination with ethanol, is seen commonly in overdose cases. Doses of several grams might be close to the maximum adsorption capacity of the standard treatment dose (50g) of activated charcoal. The aim of this study was to determine the maximum adsorption capacity for paracetamol for two types of high surface-activated charcoal [Carbomix and Norit Ready-To-Use (not yet registered trademark in Denmark) both from Norit Cosmara, Amersfoort, The Netherlands] in simulated in vivo environments: At pH 1.2 (gastric environment), at pH 7.2 (intestinal environment), and with and without 10% ethanol. METHODS: Activated charcoal, at both gastric or intestinal pHs, and paracetamol were mixed, resulting in activated charcoal-paracetamol ratios from 10:] to 1:1. In trials with ethanol, some of the gastric or intestinal fluid was replaced with an equivalent volume of ethanol, resulting in an ethanol concentration of 10% v/v. After incubation, the concentration of unabsorbed paracetamol was analyzed by high-performance liquid chromatography. The maximum adsorption capacity of paracetamol to activated charcoal was calculated as mg paracetamol adsorbed/g activated charcoal, using Langmuir's isotherm. RESULTS: Carbomix [95% confidence limits are shown in square brackets]: 623.7 [612.8;634.5] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 626.2 [611.6;640.9] mg paracetamol adsorbed/g activated charcoal (pH 7.2); Norit Ready-To-Use: 693.6 [676.8;710.5] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 722.6 [687.4;757.9] mg paracetamol adsorbed/g activated charcoal (pH 7.2). For experiments with ethanol (10% v/v) the results with Carbomix were 465.7 [449.2;482.2] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 498.6 [481.8;515.6] mg paracetamol adsorbed/g activated charcoal (pH 7.2); with Norit Ready-To-Use: 617.2 [606.6;627.7] mg paracetamol adsorbed/g activated charcoal (pH 1.2), 640.6 [624.9;656.4] mg paracetamol adsorbed/g activated charcoal (pH 7.2). CONCLUSION: Under conditions simulating immediate treatment with charcoal, a standard dose of 50 g of either of the two tested activated charcoals adsorbed a sufficient amount of paracetamol to be beneficial in the treatment of the majority of overdoses of this drug. For both types of activated charcoal, with or without ethanol, there was no significant difference in the adsorption of paracetamol at pH 1.2 and 7.2. Norit Ready-To-Use had a larger maximum adsorption capacity than Carbomix, and was not as sensitive as Carbomix to environmental changes (pH and ethanol). The presence of 10% ethanol lowered the adsorption capacity of the two tested activated charcoal preparations by an amount that might be clinically relevant in cases of intoxications by high-gram doses.